Global surface temperatures are expected to rise throughout the 21st century, and negatively impact plant growth and reproduction. Thus, it is imperative that we deepen our understanding of plant thermotolerance. The examination of native plant species that have evolved tolerance to high temperatures can provide crucial information on how plants can adapt to climate change. Boechera (Brassicaceae), a large genus that is native to North America, is highly thermotolerant, and can maintain photosynthetic activity at high temperatures. Here we report results of transcriptomic studies that seek to reveal possible thermotolerance mechanisms in B. depauperata (A.Nelson & P.B.Kenn.) Windham & Al-Shehbaz. Analysis of RNA-seq datasets from heat stressed B. depauperata and Arabidopsis thaliana (L.) Heynh. plants identified significant differences in how each of these species responds to identical heat stress conditions. The most highly upregulated heat-stress genes in A. thaliana includes the well-characterized heat-shock genes. In contrast, the Boechera heat-stress response is composed of: novel genes that lack orthologs in other genomes; genes coding for proteins of uncharacterized function; and genes coding for proteins associated with the unfolded protein and endoplasmic reticulum stress responses. In addition, genes that are protective of photosynthetic capacity are also differentially upregulated in B. depauperata.